The central goal of this program is to understand the therapeutic utility of novel strategies to induce brain tumor cell killing. The Imaging Core will play multiple diverse roles within this Program. In summary, our primary roles will be: careful analysis of cellular and molecular processes associated with apoptosis, characterization and quantification of cell types within tumors, examination of protein expression during cell death, examination of cell-cell interactions in vitro, quantitative analysis of the extent and "quality" of angiogenesis and quantification of protein expression by individual within tissues. These studies will employ the full array of current light, and potentially, electron microscopic methods including: single and multicolor fluorescence microscopy, laser confocal microscopy, digital deconvolution, liver cell imaging, transmission electron microscopy and computer-aided morphometric analyses. The Center for Biological Imaging, in which this core service will be performed, is designed for the purpose of providing state of the art microscopic technologies to its users. It is equipped to perform a continuum of optical methods including all types of light and electron microscopy essential to this Program Project. Within the scope of this project at the light microscopic level these methods include: histology, immuno-histology, live cell and in situ hybridization methods. At the electron microscopic level we will provide fine structural and immuno- electron microscopic evaluation of specimens as a natural extension of the light microscopic analysis, specifically in the characterization of cellular apoptosis. Furthermore, our considerable experience in computerized image processing and morphometry will allow quantitative analysis of observed phenomena to corroborate qualitative changes in molecular expression, cell number or morphologic appearance. This core will be used by all projects, though the imaging tools used will vary from project to project. Preliminary data have shown the validity of these approaches, and we expect a very significant increase in the use of optical techniques within the formal setting of this program.